Kinetic Resolutions - The Stoltz Group
Kinetic Resolutions - The Stoltz Group
Kinetic Resolutions - The Stoltz Group
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N3<br />
O<br />
O<br />
O<br />
Epoxide <strong>Kinetic</strong> Resolution<br />
While asymmetric epoxidation is much more practical for many compounds, some cannot be accessed in high ee<br />
through current methods<br />
In particular, terminal epoxides are difficult to get enantiopure, although the racemic epoxides are often<br />
commercially available.<br />
H2N<br />
O<br />
(±)-<br />
Yamamoto<br />
(±)-<br />
O<br />
15% recovered<br />
27% ee<br />
OTMS<br />
R<br />
R<br />
1. CSA, MeOH<br />
2. 10% Pd/C<br />
MeOH, H 2<br />
OH<br />
R<br />
(R,R)-18<br />
TMSN 3<br />
4.4 mol% 19<br />
ArOH<br />
TBME, 12-18 hr<br />
-30 to 25 o C<br />
O<br />
Catalyst 17<br />
CH 2Cl 2<br />
-30 o C, 5 h<br />
Ph<br />
O<br />
21% recovered<br />
52% ee<br />
R<br />
ArO<br />
PhO<br />
R<br />
OH<br />
R<br />
OH<br />
O<br />
O<br />
O<br />
20% epoxide recovered<br />
>95% ee<br />
TMSN 3<br />
R<br />
OTMS<br />
+<br />
O<br />
O<br />
(R)-(+)-17<br />
Epoxide <strong>Kinetic</strong> Resolution - Jacobsen<br />
+<br />
(S,S)-18<br />
R = alkyl, Bn, CH 2 Cl, c-C 6 H 11 , CH 2 OR,<br />
CH(OEt) 2 , CH 2 CN, (CH 2 ) 2 CH=CH 2<br />
2 mol% 18, 18-50 hr, 0 o C<br />
Yields > 80% (based on 1 eq TMSN 3 )<br />
ee > 90% (most > 97% ee)<br />
s = 48 - 280<br />
O<br />
O<br />
OBu<br />
Al<br />
Cl<br />
Li +<br />
Yamamoto, et. al., Tetrahedron, 1988, 44 (15), 4747<br />
N 3<br />
Wide range of Ar and R tolerated<br />
Yields usually > 95%<br />
(based on 1 eq ArOH)<br />
Typically > 90% ee<br />
Epibromohydrin (R = CH 2 Br) racemizes in presence of LiBr<br />
Dynamic <strong>Kinetic</strong> Resolution was possible!<br />
(±)-<br />
Br<br />
4 mol% 19<br />
PhOH<br />
4 mol% LiBr<br />
CH 3 CN, MS3A<br />
Br<br />
74% yield<br />
> 99% ee<br />
N N<br />
Cr<br />
t-Bu O O<br />
t-Bu<br />
t-Bu<br />
N 3<br />
N N<br />
Co<br />
t-Bu<br />
t-Bu O O<br />
t-Bu<br />
t-Bu<br />
(R,R)-18<br />
Jacobsen, et. al., J. Am. Chem. Soc., 1996, 118, 7420<br />
(R,R)-19<br />
t-Bu<br />
- OC(CF3 ) 3 + H 2 O<br />
Jacobsen, et. al., J. Am. Chem. Soc., 1999, 121, 6086<br />
20